@article{f5d1cd74140b4c8587e54707d7daad4a,
title = "Human papillomavirus 16 E6 variants differ in their dysregulation of human keratinocyte differentiation and apoptosis",
abstract = "L83V-related variants of human papillomavirus (HPV) 16 E6, exemplified by the Asian-American variant Q14H/H78Y/L83V, were shown to be more prevalent than E6 prototype in progressing lesions and cervical cancer. We evaluated functions relevant to carcinogenesis for the E6 variants L83V, R10/L83V and Q14H/H78Y/L83V as well as the prototype in a model of human normal immortalized keratinocytes (NIKS). All E6 expressing NIKS equally abrogated growth arrest and DNA damage responses. Organotypic cultures derived from these keratinocytes demonstrated hyperplasia and aberrantly expressed keratin 5 in the suprabasal compartment. In contrast, differentiation and induction of apoptosis varied. The E6 variant rafts expressed keratin 10 in nearly all suprabasal cells while the prototype raft showed keratin 10 staining in a subset of suprabasal cells only. In addition, E6 variant NIKS expressing R10G/L83V and Q14H/H78Y/L83V were more prone to undergo cell-detachment-induced apoptosis (anoikis) than NIKS expressing E6 prototype. The combined differentiation and apoptosis pattern of high-risk E6 variants, especially of Q14H/H78Y/L83V, may reflect a phenotype beneficial to carcinogenesis and viral life cycle.",
keywords = "Apoptosis, Differentiation, E6 prototype, E6 variant, Human papillomavirus 16, Keratinocyte, Proliferation",
author = "Ingeborg Zehbe and Christina Richard and DeCarlo, {Correne A.} and Anny Shai and Lambert, {Paul F.} and Hava Lichtig and Massimo Tommasino and Levana Sherman",
note = "Funding Information: We are grateful to Dr. Ilan Tsarfaty from the Department of Human Microbiology at the Sackler School of Medicine for his assistance in tissue staining image analysis and to the staff from the Central Laboratory at the Thunder Bay Regional Health Sciences Centre for cutting and staining sections. This work was mainly funded by the Deutsche Forschungsgemeinschaft SFB 432-A9 and the Northern Cancer Research Foundation (both awarded to I Zehbe). Additional funding is acknowledged from the Israel's Ministry of Science, Culture and Sport (MOST), Project No.1841 (awarded to L Sherman) and NIH grants CA098428 and CA022443 (both awarded to PF Lambert). ",
year = "2009",
month = jan,
day = "5",
doi = "10.1016/j.virol.2008.09.036",
language = "אנגלית",
volume = "383",
pages = "69--77",
journal = "Virology",
issn = "0042-6822",
publisher = "Academic Press Inc.",
number = "1",
}